oject Summary: The Molecular Biophysics Graduate Program provides UCSF students with a unique opportunity to bring methodologies and approaches from physics, mathematics, chemistry and engineering to bear on the most sophisticated problems in quantitative biology in a stellar biomedical environment. The program emphasizes interdisciplinary training, and a hallmark of the program is the use of experimental and computational approaches to address fundamental questions in molecular function and cellular processes. We feel it is imperative to train the next generation of scientists not only to understand the biology and structural biology but also to be able to synthesize vast amounts of information into quantitative and testable models. Reflecting these scientific opportunities and needs, we have expanded our efforts in computational biophysics while maintaining a solid emphasis on the physical basis for complex biological behavior. As a consequence we have changed the title of this application from Structural Biology to Molecular Biophysics to acknowledge the importance of training students in a broad array of approaches ranging from structural biology to computational chemistry to bioinformatics to systems biology. To provide a more integrated inter-disciplinary training experience and specifically encourage disciplinary cross-over, our unique training program has evolved to focus on very rapidly bringing all students to a common understanding, breaking down sociological barriers to interdisciplinary research, building confidence and enhancing bonding within the entering class. This is coupled with our traditional strong emphasis on critical thinking, careful mentoring, building communication skills, and the benefits of collaborative research. Relevance: The extraordinary complexity of biological systems ultimately derives from the properties of individual molecules and how they interact to form supramolecular machines and networks. To provide new insight into this complexity, the UCSF Molecular biophysics training grant will train a new generation of scientists to simultaneously understand the physical basis for molecular behavior and to have the tools required for integrating the vast amounts of available information into testable quantitative models of overall function.